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Palacios, Igor

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Palacios

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Igor

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Palacios, Igor
Author's Publications: search.filters.isAuthorOfPublication.364fd722-a1f2-4401-b16f-8d4ee1060513

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    Metabolite Profiles Predict Acute Kidney Injury and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement
    (John Wiley and Sons Inc., 2016) Elmariah, Sammy; Farrell, Laurie A.; Daher, Maureen; Shi, Xu; Keyes, Michelle J.; Cain, Carolyn H.; Pomerantsev, Eugene; Vlahakes, Gus; Inglessis, Ignacio; Passeri, Jonathan; Palacios, Igor; Fox, Caroline S.; Rhee, Eugene; Gerszten, Robert
    Background: Acute kidney injury (AKI) occurs commonly after transcatheter aortic valve replacement (TAVR) and is associated with markedly increased postoperative mortality. We previously identified plasma metabolites predictive of incident chronic kidney disease, but whether metabolite profiles can identify those at risk of AKI is unknown. Methods and Results: We performed liquid chromatography–mass spectrometry–based metabolite profiling on plasma from patients undergoing TAVR and subjects from the community‐based Framingham Heart Study (N=2164). AKI was defined by using the Valve Academic Research Consortium‐2 criteria. Of 44 patients (mean age 82±9 years, 52% female) undergoing TAVR, 22 (50%) had chronic kidney disease and 9 (20%) developed AKI. Of 85 metabolites profiled, we detected markedly concordant cross‐sectional metabolic changes associated with chronic kidney disease in the hospital‐based TAVR and Framingham Heart Study cohorts. Baseline levels of 5‐adenosylhomocysteine predicted AKI after TAVR, despite adjustment for baseline glomerular filtration rate (odds ratio per 1‐SD increase 5.97, 95% CI 1.62–22.0; P=0.007). Of the patients who had AKI, 6 (66.7%) subsequently died, compared with 3 (8.6%) deaths among those patients who did not develop AKI (P=0.0008) over a median follow‐up of 7.8 months. 5‐adenosylhomocysteine was predictive of all‐cause mortality after TAVR (hazard ratio per 1‐SD increase 2.96, 95% CI 1.33–6.58; P=0.008), independent of baseline glomerular filtration rate. Conclusions: In an elderly population with severe aortic stenosis undergoing TAVR, metabolite profiling improves the prediction of AKI. Given the multifactorial nature of AKI after TAVR, metabolite profiles may identify those patients with reduced renal reserve.
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    Proteomic signatures of serum albumin-bound proteins from stroke patients with and without endovascular closure of PFO are significantly different and suggest a novel mechanism for cholesterol efflux
    (Springer Berlin Heidelberg, 2015) Lopez, Mary F; Krastins, Bryan; Sarracino, David A; Byram, Gregory; Vogelsang, Maryann S; Prakash, Amol; Peterman, Scott; Ahmad, Shadab; Vadali, Gouri; Deng, Wenjun; Inglessis, Ignacio; Wickham, Tom; Feeney, Kathleen; Dec, G William; Palacios, Igor; Buonanno, Ferdinando; Lo, Eng; Ning, MingMing
    Background: The anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation – altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure. Methods: The method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure. Results: The results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions. Conclusions: The collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions. Electronic supplementary material The online version of this article (doi:10.1186/1559-0275-12-2) contains supplementary material, which is available to authorized users.